Identification of eosinophil lineage-committed progenitors in the murine bone marrow

Hiromi Iwasaki, Shin Ichi Mizuno, Robin Mayfield, Hirokazu Shigematsu, Yojiro Arinobu, Brian Seed, Michael F. Gurish, Kiyoshi Takatsu, Koichi Akashi

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5Rα+CD34+c-Kitlo phenotype. Normal bone marrow cells also contained IL-5Rα+CD34 +c-Kitlo EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5Rα in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Rα+ GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Rα might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils. JEM

Original languageEnglish
Pages (from-to)1891-1897
Number of pages7
JournalJournal of Experimental Medicine
Volume201
Issue number12
DOIs
Publication statusPublished - Jun 20 2005

Fingerprint

Eosinophils
Bone Marrow
Monocytes
Granulocyte Precursor Cells
Mast Cells
Neutrophils
Eosinophil Major Basic Protein
Eosinophil Peroxidase
Basophils
Helminths
Interleukin-5
Bone Marrow Cells
Peptide Hydrolases
Transcription Factors
Phenotype
Infection

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Identification of eosinophil lineage-committed progenitors in the murine bone marrow. / Iwasaki, Hiromi; Mizuno, Shin Ichi; Mayfield, Robin; Shigematsu, Hirokazu; Arinobu, Yojiro; Seed, Brian; Gurish, Michael F.; Takatsu, Kiyoshi; Akashi, Koichi.

In: Journal of Experimental Medicine, Vol. 201, No. 12, 20.06.2005, p. 1891-1897.

Research output: Contribution to journalArticle

Iwasaki, H, Mizuno, SI, Mayfield, R, Shigematsu, H, Arinobu, Y, Seed, B, Gurish, MF, Takatsu, K & Akashi, K 2005, 'Identification of eosinophil lineage-committed progenitors in the murine bone marrow', Journal of Experimental Medicine, vol. 201, no. 12, pp. 1891-1897. https://doi.org/10.1084/jem.20050548
Iwasaki, Hiromi ; Mizuno, Shin Ichi ; Mayfield, Robin ; Shigematsu, Hirokazu ; Arinobu, Yojiro ; Seed, Brian ; Gurish, Michael F. ; Takatsu, Kiyoshi ; Akashi, Koichi. / Identification of eosinophil lineage-committed progenitors in the murine bone marrow. In: Journal of Experimental Medicine. 2005 ; Vol. 201, No. 12. pp. 1891-1897.
@article{ee56441fd96d4bc5b4b33e6991356aa8,
title = "Identification of eosinophil lineage-committed progenitors in the murine bone marrow",
abstract = "Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5Rα+CD34+c-Kitlo phenotype. Normal bone marrow cells also contained IL-5Rα+CD34 +c-Kitlo EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5Rα in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Rα+ GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Rα might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils. JEM",
author = "Hiromi Iwasaki and Mizuno, {Shin Ichi} and Robin Mayfield and Hirokazu Shigematsu and Yojiro Arinobu and Brian Seed and Gurish, {Michael F.} and Kiyoshi Takatsu and Koichi Akashi",
year = "2005",
month = "6",
day = "20",
doi = "10.1084/jem.20050548",
language = "English",
volume = "201",
pages = "1891--1897",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "12",

}

TY - JOUR

T1 - Identification of eosinophil lineage-committed progenitors in the murine bone marrow

AU - Iwasaki, Hiromi

AU - Mizuno, Shin Ichi

AU - Mayfield, Robin

AU - Shigematsu, Hirokazu

AU - Arinobu, Yojiro

AU - Seed, Brian

AU - Gurish, Michael F.

AU - Takatsu, Kiyoshi

AU - Akashi, Koichi

PY - 2005/6/20

Y1 - 2005/6/20

N2 - Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5Rα+CD34+c-Kitlo phenotype. Normal bone marrow cells also contained IL-5Rα+CD34 +c-Kitlo EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5Rα in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Rα+ GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Rα might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils. JEM

AB - Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5Rα+CD34+c-Kitlo phenotype. Normal bone marrow cells also contained IL-5Rα+CD34 +c-Kitlo EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5Rα in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Rα+ GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Rα might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils. JEM

UR - http://www.scopus.com/inward/record.url?scp=22344443951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22344443951&partnerID=8YFLogxK

U2 - 10.1084/jem.20050548

DO - 10.1084/jem.20050548

M3 - Article

VL - 201

SP - 1891

EP - 1897

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 12

ER -